Antigen-specific release of beta-chemokines by anti-HIV-1 cytotoxic T lymphocytes.
A major advance in understanding human immunodeficiency virus (HIV) biology was the discovery that the beta-chemokines MIP-1 alpha (macrophage inflammatory protein-1 alpha), MIP-1 beta (macrophage inflammatory protein-1 beta) and RANTES (regulated on activation, normal T-cell expressed and secreted)...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
1998
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| _version_ | 1797103953981210624 |
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| author | Price, D Sewell, A Dong, T Tan, R Goulder, P Rowland-Jones, S Phillips, R |
| author_facet | Price, D Sewell, A Dong, T Tan, R Goulder, P Rowland-Jones, S Phillips, R |
| author_sort | Price, D |
| collection | OXFORD |
| description | A major advance in understanding human immunodeficiency virus (HIV) biology was the discovery that the beta-chemokines MIP-1 alpha (macrophage inflammatory protein-1 alpha), MIP-1 beta (macrophage inflammatory protein-1 beta) and RANTES (regulated on activation, normal T-cell expressed and secreted) inhibit entry of HIV-1 into CD4+ cells by blocking the critical interaction between the CCR5 coreceptor and the V3 domain of the viral envelope glycoprotein gp120 [1,2]. CD8+ lymphocytes are a major source of beta-chemokines [3], but the stimulus for chemokine release has not been well defined. Here, we have shown that engagement of CD8+ cytotoxic T lymphocytes (CTLs) with HIV-1-encoded human leukocyte antigen (HLA) class I-restricted peptide antigens caused rapid and specific release of these beta-chemokines. This release paralleled cytolytic activity and could be attenuated by naturally occurring amino acid variation within the HLA class I-restricted peptide sequence. Epitope variants that bound to appropriate HLA class I molecules but failed to stimulate cytolytic activity in CTLs also failed to stimulate chemokine release. We conclude that signalling through the T-cell receptor (TCR) following binding of antigen results in beta-chemokine release from CTLs in addition to cytolytic activity, and that both responses can be abolished by epitope mutation. These results suggest that antigenic variation within HIV-1 might not only allow the host cell to escape lysis, but might also contribute to the propagation of infection by failing to activate beta-chemokine-mediated inhibition of HIV-1 entry. |
| first_indexed | 2024-03-07T06:27:22Z |
| format | Journal article |
| id | oxford-uuid:f4c81f99-651f-47ff-ab8c-965eb60c33b7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:27:22Z |
| publishDate | 1998 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:f4c81f99-651f-47ff-ab8c-965eb60c33b72022-03-27T12:22:24ZAntigen-specific release of beta-chemokines by anti-HIV-1 cytotoxic T lymphocytes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f4c81f99-651f-47ff-ab8c-965eb60c33b7EnglishSymplectic Elements at OxfordElsevier1998Price, DSewell, ADong, TTan, RGoulder, PRowland-Jones, SPhillips, RA major advance in understanding human immunodeficiency virus (HIV) biology was the discovery that the beta-chemokines MIP-1 alpha (macrophage inflammatory protein-1 alpha), MIP-1 beta (macrophage inflammatory protein-1 beta) and RANTES (regulated on activation, normal T-cell expressed and secreted) inhibit entry of HIV-1 into CD4+ cells by blocking the critical interaction between the CCR5 coreceptor and the V3 domain of the viral envelope glycoprotein gp120 [1,2]. CD8+ lymphocytes are a major source of beta-chemokines [3], but the stimulus for chemokine release has not been well defined. Here, we have shown that engagement of CD8+ cytotoxic T lymphocytes (CTLs) with HIV-1-encoded human leukocyte antigen (HLA) class I-restricted peptide antigens caused rapid and specific release of these beta-chemokines. This release paralleled cytolytic activity and could be attenuated by naturally occurring amino acid variation within the HLA class I-restricted peptide sequence. Epitope variants that bound to appropriate HLA class I molecules but failed to stimulate cytolytic activity in CTLs also failed to stimulate chemokine release. We conclude that signalling through the T-cell receptor (TCR) following binding of antigen results in beta-chemokine release from CTLs in addition to cytolytic activity, and that both responses can be abolished by epitope mutation. These results suggest that antigenic variation within HIV-1 might not only allow the host cell to escape lysis, but might also contribute to the propagation of infection by failing to activate beta-chemokine-mediated inhibition of HIV-1 entry. |
| spellingShingle | Price, D Sewell, A Dong, T Tan, R Goulder, P Rowland-Jones, S Phillips, R Antigen-specific release of beta-chemokines by anti-HIV-1 cytotoxic T lymphocytes. |
| title | Antigen-specific release of beta-chemokines by anti-HIV-1 cytotoxic T lymphocytes. |
| title_full | Antigen-specific release of beta-chemokines by anti-HIV-1 cytotoxic T lymphocytes. |
| title_fullStr | Antigen-specific release of beta-chemokines by anti-HIV-1 cytotoxic T lymphocytes. |
| title_full_unstemmed | Antigen-specific release of beta-chemokines by anti-HIV-1 cytotoxic T lymphocytes. |
| title_short | Antigen-specific release of beta-chemokines by anti-HIV-1 cytotoxic T lymphocytes. |
| title_sort | antigen specific release of beta chemokines by anti hiv 1 cytotoxic t lymphocytes |
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